Abstract Body (Do not enter title and authors here): Social isolation (9.2%-14.4% prevalence) and loneliness (~25% prevalence) are global public health concerns. This prospective cohort study quantifies their impact on all-cause and cardiovascular mortality in patients with pre-existing cardiovascular disease (CVD). We analyzed 150,543 UK Biobank participants with baseline CVD (coronary heart disease, hypertension, myocardial infarction, or stroke). Social isolation was assessed using a composite score (household members, social activities, contact frequency), and loneliness via self-reported questionnaires. Cox models examined mortality risks over 13.5 years median follow-up, adjusted for sociodemographic, clinical, and lifestyle factors. Extreme social isolation increased all-cause mortality risk by 47% (HR 1.47, 95% CI 1.40-1.53) and cardiovascular mortality by 50% (HR 1.50, 95% CI 1.40-1.62), accounting for 29-33% of population-attributable deaths. Loneliness independently raised all-cause mortality by 19% (HR 1.19, 95% CI 1.12-1.26; PAF 28.06%) and cardiovascular mortality by 22% (HR 1.22, 95% CI 1.11-1.35; PAF 34.41%). For CVD subtypes, extreme isolation increased coronary heart disease mortality by 54% (HR 1.54, 95% CI 1.41-1.68), hypertension-related death by 42% (HR 1.42, 95% CI 1.26-1.61), and myocardial infarction mortality by 39% (HR 1.39, 95% CI 1.19-1.64). Concurrent isolation and loneliness synergistically elevated cardiovascular mortality risk by 33% (HR 1.33, 95% CI 1.14-1.57). Kaplan-Meier analyses confirmed significantly diverging cumulative mortality curves over 16 years (log-rank p < 0.0001). Social isolation and loneliness independently and jointly contribute to substantial mortality in CVD patients, accounting for 28%-38% of deaths. These findings establish psychosocial factors as modifiable risk predictors comparable to biomedical risks, necessitating integration into cardiovascular risk assessment and targeted interventions.